Downloaded 49 times
Uploaded byDr. Koppala R.V.S. Chaitanya
opioid anlagesic and its antagonist
The document discusses various opioid analgesics including their mechanisms of action, effects, and therapeutic uses. It describes how opioids like morphine and pethidine work in the central nervous system to provide analgesia and other effects through binding to mu, kappa, and delta opioid receptors. It also covers the pharmacokinetics, indications, adverse effects and classifications of different opioid drugs.
More Related Content
Similar to opioid anlagesic and its antagonist
More from Dr. Koppala R.V.S. Chaitanya
opioid anlagesic and its antagonist
- 1. Opioid Analgesics Mr. RVSChaitanya Koppala Lovely professional university, Punjab
- 2. Opioid Analgesics (against algesia)– some important terms • Analgesics: Are the Drugs which selectively relieves pain by acting in the CNS or on peripheral pain mechanisms, without significantly altering the consciousness – Opioids and NSAIDS • Opioids: Any drug which binds to the opioid receptors (Pharmacologically related) in the CNS and antagonized by Naloxone . They may be – Natural, Synthetic and semi- synthetic • Opiates: Drugs derived from opium – Natural or semi- synthetic • Narcotics: Drugs derived from opium or opium like compounds, with potent analgesic effects associated with significant alteration of mood and behavior, and with the potential for dependence and tolerance following repeated administration.
- 3. Opioids - Opium •A dark brown, resinous material obtained from poppy (Papaver somniferum) Capsules. OPIUM PHENANTHRENE •Morphine 9-14% •Codeine 0.5-2% •Thebaine 0.2-1% BENZYLISOQUINOLINE •Papaverine 0.8-1% •Noscapine 3-10% •Narcine 0.2-0.4%
- 4. Poppy Plant -image
- 5. MORPHINE (Pharmacological actions) -CNS • Analgesia: • Strong analgesic • Visceral pain is relieved better than somatic pain • Degree of analgesia increases with dose • Nociceptive pain is better relieved than Neuretic pain • Associated reactions to pain are also relieved – apprehension, fear and autonomic effects • Tolerance to pain is better
- 6. MORPHINE – Analgesia action •Two components – spinal and supraspinal • Inhibits release of excitatory transmitters from primary afferents – at Substantia gelatinosa of dorsal horn • Exerted through Interneurones – gating of pain • At supraspinal level in cortex, meidbrain and medulla - alter processing and interpretation and send inhibitory impulses through descending pthway
- 7. Pharmacological actions of Morphine(CNS) – contd. • Sedation: – Drowsiness and indifference to surroundings – Inability to concentrate and extravagant imagination – colorful day dream – Apparent excitement – Larger doses produce sleep – EEG resembles normal sleep • Mood effects: – In Normal persons calming effect, mental clouding, feeling of detachment, lack of initiative etc. - unpleasant in absence of pain – Sometimes DYSHORIA – But in persons with pain & addicts sense of wellbeing, pleasurable floating feelings – kick – EUPHORIA
- 8. Pharmacological actions of Morphine(CNS) – contd. • Depression: 1. Respiratory centre depression – Both rate and depth of respiration are diminished • Dangerous in Head injury and asthmatics 1. Cough Centre – Depressed 2. Temperature regulating centre – depressed 3. Vasomotor centre – high doses cause fall in BP • Stimulation: 1. CTZ – sensitize CTZ to vestibular and other impulses 2. Edinger Westphal Nucleus – miosis 3. Vagal centre – Bradycardia 4. Hippocampal cells – convulsions (inhibition of GABA release)
- 9. Pharmacological actions of Morphine– contd. • Neuro-endocrine: • GnRH and CRH are inhibited – FSH, LH and ACTH levels are lowered – only short term – tolerance develops • Decrease in levels of Sex hormone and corticosteroids, but no infertility • Increases ADH release – oliguria • CVS: NO DIRECT EFFECT ON HEART • Vasodilatation – histamine release, depression of vasomotor centre and directly on blood vessels decreasing the tone • Cardiac work reduction due to consistent vasodilatation
- 10. Pharmacological actions of Morphine– contd. • GIT: CONSTIPATION • Due to direct action on intestine reducing propulsive movement, spasm of sphincters, decrease in all GIT secretions • Smooth Muscles: • Billiary Tract: Billiary colic – closure of sph. Of Oddi • Bladder: Urinary urgency but difficulty • Bronchi - Bronchospasm
- 11. Morphine - Pharmacokinetics • Absorptionand Distribution: • Variable orally (usually not given orally – 1st pass metabolism, given IM or IV) • Widely distributed – liver, spleen, kidney etc. • Enters Brain slowly • Readily crosses placental barrier – dependence in fetus • Metaboloism: • In Liver by glucoronidation – water soluble metabolites • Morphine-6- Glucoronide – analgesic – in renal failure prolong analgesia • Morphine-3-glucoronide – No analgesia – neuroexcitatory • Excretion: • Via Urine, Plasma t1/2 = 2-3 Hrs • Action lasts for 4-6 Hrs • Completely eliminated in 24 Hrs • Preparation: 10, 15, and 20 mg. (IV: 2 – 10 mg)
- 12. Morphine – Adverse Effects 1.Respiratory Depression: Infant and Old 2. Vomiting 3. Sedation, Mental Clouding – sometimes dysphoria 4. Hypotensive effect 5. Rise in Intracranial Pressure 6. Apnoea: Newborn 7. Urinary retention 8. Idiosyncrasy and allergy 9. Acute Morphine Poisoning: occurs if >50 mg (Lethal dose – 250 mg), Gastric lavage with KMNO4, Specific antidote: Naloxone: 0.4 to 0.8 mg IV repeatedly in 2-3 minutes till respiration picks up 10. Tolerance and dependence
- 13. Morphine – Therapeutic uses •Analgesic: 1. Long Bone Fracture 2. Myocardial Infarction 3. Terminal stages of cancer 4. Burn patients 5. Postoperative patients 6. Visceral pains – pulmonary embolism, pleurisy, acute pericarditis 7. Biliary colic and renal colic 8. Obstetric analgesia 9. Segmental analgesia
- 14. Morphine – Other Therapeuticuses • Preanaesthetic Medication • Balanced anaesthesia and surgical analgesia • Acute Left ventricular failure – Cardiac asthma • Cough – not used but Codeine is used • Diarrhoea – colostomy - Loperamide, Diphenoxylate
- 15. Morphine - Contraindications 1. TwoExtremes of Age 2. Bronchial asthma 3. Respiratory insufficiency - empysema 4. Head Injury 5. Shock – Hypotension 6. Undiagnosed acute abdomen 7. BHP 8. Renal Failure, Liver diseases and hypothyrodism 9. Unstable personalities
- 16. Opioids - Classification 1.Natural Opium Alkaloids: Morphine and Codeine 2. Semi-synthetic: Diacetylmorphine (Heroin) and Pholcodeine 3. Synthetic Opioids: • Phenylpiperidines: • Pethidine (Mepiridine) and its congeners – Diphenoxylate and Loperamide • Fentanyl and its congeners – sufentanil, remifentanil and alfentanil • Phenyl-heptylmines: Methadone and congeners like Propoxyphene and Dextropropoxyphene • Benzomorphans: Pentazocine • Morphinan compounds and congeners: Levorphanol and Butorphanol
- 17. Pethidine • Morphine VsPethidine: – 1/10th as potent as Morphine, but Efficacy is similar – Produces as much sedation, euphoria and respiratory depression in equianalgesic dose and similar abuse potential – Less spasmodic action in smooth muscles – less miosis, constipation and urinary retention – Rapid but short duration of action (2-3 Hrs) – Vagolytic effect - Tachycardia – Devoid of antitussive action – Less histamine release – safer in asthmatics – Better oral absorption
- 18. Pethidine – contd. •Pharmacokinetics – Well absorbed orally, bioavailability 50% – Effects appear in 10-15 min. after oral absorption – On parenteral administration action lasts for 2-3 Hrs – Metabolized in liver – mepiridinic acid and norpethidine – Norpethidine accumulates on chronic use – Excreted in urine
- 19. Pethidine – contd. •Adverse Effects: • Similar to Morphine • Atropine like effects – dry mouth, blurred vision, tachycardia • Overdose – tremors, mydriasis, delirium and convulsion due to norpethidine accumulation • Uses: • Analgesic as substitute of Morphine • Ptreanaesthetic medication • As analgesic during labour – less fetal respiratory depression • Dose 50-100 mg IM/SC, oral – 50-100 mg tabs.
- 20. Opioid Receptors • Mainly3 (three) types of receptors – μ (mu), κ (kappa) and δ (delta) • Subtypes: μ1, μ2, κ1, κ2, κ3, δ1 and δ2 • Location: Peripheral Nerve endings, SG in spinal chord, Periaqueductal gray (PAG) in midbrain and Brain stem (medulla, hypothalumus and also amygdala • Opioids are – agonists, partial agonist or competitive antagonists of these receptors • Overall effect depends on nature of interaction and affinity to these • Morphine is agonist of all but affinity is higher for mu
- 21. μ receptor κreceptor δ receptor Location μ1 – supraspinal μ2 - spinal κ1 – spinal κ3 -supraspinal Spinal supraspinal Effects Analgesia Respiratory depression Sedation Euphoria Miosis Physical dependence Loss of GI motility Spinal analgesia Dysphoria Sedation Psychomimetic Physical dependence (nalorphine type) Spinal analgesia Affective behaviour (Supraspinal) Respiratory depression Reduced GI motility Agonists Morphine, Codeine, Fentanyl and pentazocine weakly Pentazocine Effects of Different Opioid Receptor Stimulation:
- 22. Opioid Receptors – Intracellularmechanism • All are G-protein coupled receptors • Located on prejunctional neurones • Inhibits release of transmitters – NA, DA, 5-HT, GABA and Glutamate • Activation reduces intracellular cAMP formation - Opening of K+ channel via μ and δ. and supression of N type of Ca++ channels • Ultimately Hyperpolarization and reduced intracellular Ca++ Reduced Neurotransmitter release
- 23. Opioid Antagonists 1. Pureantagonists: Naloxone, Naltrexone and Nalmefene • Affinity for all receptors (μ, δ and κ) • Can displace opioids bound to α-receptors • No action on Normal person but reverses poisoning and withdrawal symptoms in addicts 1. Mixed Agonist-antagonists: Nalorphine, Pentazocine, Butorphanol and Nalbuphine 2. Partial/weak μ agonist and κ antagonist: Buprenorphine
- 24. Nalorphine • Not usedanymore • Previously used as Opioid antagonist • But, antagonism is restricted to μ- receptor only and agonist of κ- receptor • Drawbacks - dysphoria and psychomimetic effects
- 25. Pentazocine • Weak α-receptorantagonist, but agonist of κ-receptor • One of the commonly used agents, given orally and IM • Low abuse liability • Pharmacokinetics: – High 1st pass metabolism but effective orally – Half life = 3-4 Hrs – Metabolized in liver by glucoronide conjugation – Dose: orally 50-100 mg and parenterally 30-60 mg IM • Uses:Moderately severe pain in Injury, Burns, Fracture Trauma, Cancer and Orthopaedic manuevers (Fortwin, Fortagesic)
- 26. Pentazocine Vs Morphine •Spinal analgesia via kappa receptor • Dose is 30 mg Vs 10 mg and low ceiling effect • Sedation and Respiratory depression at lower doses • Tachycardia and rise in BP – dangerous in MI • Lesser smooth muscle spasms • Vomiting and other side effects are less • Subjective effects – lower ceiling (psycomimetic effects) • Tolerance develops on repeated use, but lesser than Morphine • Withdrawal symptoms – both Morphine and Nalorphine like • Good analgesic in subjects not exposed to Morphine • Precipitate withdrawal – in Morphine addicts
Editor's Notes
- #3 Narcotic is a greek term meanig stupor(deficiency of mental and physical alertness) pethidine, fentanyl, sufentanyl and alfentanyl are synthetic.
- #4 Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings--as the above formula shows. Phenanthrene has five resonance structures, given below. Reactions of phenanthrene typically occur at the 9 and 10 positions. Many benzylisoquinolines have a methylated nitrogen atom as well as functional groups containing oxygen (-OH, -OCH3, -OCH2O-) in positions 6, 7, 3' and 4'
- #13 Tolerance and dependence is the most comon problem with morphine. Tolerance is exhibited in most action except constipation and miotic action. It produces psychological and physical dependence Because of this abuse potential increases. Mostly medical and paramedical persons go for morphine abuse. This is the major drawback of morphine. Withdrawal may lead to Drug seeking behaviour and may turn to Morphine withdrawal syndrome. It is characterized by anxiety, fear, restlesness, diarrhoea, abdominal coli, delirium and convulsion - treatment is methadone.